4U5C

Crystal structure of GluA2, con-ikot-ikot snail toxin, partial agonist FW and postitive modulator (R,R)-2b complex

4U5C の概要

• エントリーDOI: 10.2210/pdb4u5c/pdb
• 分子名称: Glutamate receptor 2, Con-ikot-ikot, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: ampa receptor, transport protein-toxin complex, transport protein/toxin
• 由来する生物種: Rattus norvegicus (Rat); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 387762.41

構造登録者

Chen, L.,Gouaux, E. (登録日: 2014-07-25, 公開日: 2014-08-13, 最終更新日: 2024-11-13)

主引用文献

Chen, L.,Durr, K.L.,Gouaux, E.
X-ray structures of AMPA receptor-cone snail toxin complexes illuminate activation mechanism.
Science, 345:1021-1026, 2014

PubMed Abstract: AMPA-sensitive glutamate receptors are crucial to the structural and dynamic properties of the brain, to the development and function of the central nervous system, and to the treatment of neurological conditions from depression to cognitive impairment. However, the molecular principles underlying AMPA receptor activation have remained elusive. We determined multiple x-ray crystal structures of the GluA2 AMPA receptor in complex with a Conus striatus cone snail toxin, a positive allosteric modulator, and orthosteric agonists, at 3.8 to 4.1 angstrom resolution. We show how the toxin acts like a straightjacket on the ligand-binding domain (LBD) "gating ring," restraining the domains via both intra- and interdimer cross-links such that agonist-induced closure of the LBD "clamshells" is transduced into an irislike expansion of the gating ring. By structural analysis of activation-enhancing mutants, we show how the expansion of the LBD gating ring results in pulling forces on the M3 helices that, in turn, are coupled to ion channel gating.

PubMed: 25103405
DOI: 10.1126/science.1258409

実験手法

X-RAY DIFFRACTION (3.6883 Å)